Acquired Immune Deficiency Syndrome is a pandemic immunosuppressive disease which results in life threatening opportunistic infections and malignancies. A retrovirus, designated human immunodeficiency virus (HIV-1(HTLV-III LAV)), has been isolated and identified as the etiologic agent of this disease. This virus has been shown to be harbored by T helper lymphocytes and monocyte-macrophages, and it is detectable in whole blood, plasma, lymphatic fluid, serum, semen, saliva and central nervous system tissue. Ho et al., New England Journal of Medicine, 321:1621-1625 (1989). Although cells of the monocyte-macrophage lineage serve as important reservoirs of HIV infection, most of the cell-associated virus in the blood is contained within CD4+ T cells. Characteristically, then, AIDS is associated with a progressive depletion of T cells, especially the helper-inducer subset bearing the OKT4 surface marker.
Several agents have been reported to inhibit the growth of the human immunodeficiency virus in vitro. Among the agents exhibiting in vitro anti-HIV activity, some are now in clinical use, including ribavirin, zidovudine (AZT), the 2', 3'-dideoxynucleosides (DDI and DDC); ganciclovir alpha-interferon, interleukin-2, ampligen and isoprinosine. Anand et al., Lancet i,97-98 (1986); Balzarini et al., Int. J. Cancer 37:451-457 (1986); Ho et al., Lancet, i,602-604 (1985); McCormick et al., Lancet ii,1367-1369 (1984); Mitchell et al., Lancet i,890-892 (1987); Mitsuya et al., Proc. Natl. Acad. Sci. USA 83:1911-1915 and 82:7096-7100 (1985, 1986); Mitsuya et al., Science 226:172-174 (1984); Pert et al., Proc. Natl. Acad. Sci. USA 83:9254-9258 (1986); Pizzi et al., Human Biol. 22:151-190 (1950); Rozenbaum et al., Lancet i,450-451 (1985); Sandstrom et al., Lancet i,1480-1482 (1986); Veno and Kino, Lancet i,1379 (1987); Yamamoto et al., Interferon Res. 6:143-152 (1986), and Antiviral Research 7:127-137 (1987). However, no therapy to date is known to cure AIDS.
The majority of the compounds tested for use against HIV. including those referenced above, appear to be either too toxic for prolonged use or incapable of completely eliminating HIV infection from the human host. Blanche et al., Lancet i,863 (1986); De Clercq et al., J. Med. Chem. 29:1561-1569 (1986); Yarchoan et al., Lancet i,575-580 (1986); Wetterberg et al., Lancet i,159 (1987). In view of the severity of the AIDS situation and the toxicity and limited clinical efficacy of the compounds tested thus far, the scientists of the present invention have begun investigating the anti-HIV activity of extracts from Chinese medicinal herbs. Chang and Yeung, Antiviral Research 9:163-176 (1988); Chang et al., Antiviral Research 11:263-73 (1989). This interest in Chinese herbs was prompted by Chinese folklore, wherein a number of these herbs have been reputed to have anti-infective activity and to be well tolerated by humans. A subset of these herbs now also appear to exhibit anti-HIV activity, and are disclosed herein.
However, Chinese folk medicine is based largely on anecdotal observations spanning the past several thousands of years. Hence, the effectiveness of the medicinal herbs used by folk medicine practitioners has, for the most part, not been substantiated by scientific methods. Despite this lack of scientific proof, it is quite possible that some herbal remedies may have specific therapeutic action, as was proven to be the case with the anti-malarial. qinghaosu, and perhaps even anti-HIV activity. Klayman, Science, 228:1049-1055 (1985). Consequently, with regard to the possible anti-HIV activity among Chinese herbal extracts, an urgent need exists for: 1) the identification of effective anti-HIV herbal extracts, 2) the substantive documentation, by modern scientific methods, of the effectiveness of these herbal extracts against HIV, and 3) the identification of effective anti-HIV Chinese herbal extracts that are less toxic than the currently available anti-HIV agents. The present invention satisfies this need and provides related advantages as well.
The papers cited throughout this application are incorporated herein by reference.